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Study of Pembrolizumab (MK-3475) in Participants With Advanced Urothelial Cancer (MK-3475-052/KEYNOTE-052)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02335424
Recruitment Status : Active, not recruiting
First Posted : January 9, 2015
Results First Posted : July 5, 2019
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

This is a study using pembrolizumab (MK-3475, KEYTRUDA®) for first-line treatment of participants with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. The primary study objective is to determine the objective response rate (ORR) in all participants and by programmed cell death ligand 1 (PD-L1) status.

With Amendment 4, once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.


Condition or disease Intervention/treatment Phase
Urothelial Cancer Biological: pembrolizumab Phase 2

Detailed Description:
Participants receiving pembrolizumab who attain a complete response (CR) may consider stopping trial treatment if they meet criteria for holding therapy. Participants who stop trial treatment after receiving 24 months of trial treatment for reasons other than progressive disease (PD) or intolerability, or participants who attain a CR and stop trial treatment may be eligible for up to one year of retreatment upon experiencing PD.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 374 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial of Pembrolizumab (MK-3475) in Subjects With Advanced/Unresectable or Metastatic Urothelial Cancer
Actual Study Start Date : February 24, 2015
Actual Primary Completion Date : June 19, 2018
Estimated Study Completion Date : November 10, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab
Participants receive pembrolizumab, 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to 24 months.
Biological: pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®




Primary Outcome Measures :
  1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months) ]
    ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented.

  2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months) ]
    ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥1% CPS and experienced a CR or PR per RECIST 1.1 is presented.

  3. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months) ]
    ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 strong positive expression of ≥10% CPS and experienced a CR or PR per RECIST 1.1 is presented.


Secondary Outcome Measures :
  1. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a confirmed CR or PR is presented.

  2. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    DOR was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a PD-L1 positive expression of ≥1% CPS and who had a confirmed CR or PR is presented.

  3. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    DOR was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a PD-L1 strong positive expression of ≥10% CPS and who had a confirmed CR or PR is presented.

  4. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    PFS was determined in all participants. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants is presented.

  5. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    PFS was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants who had a PD-L1 positive expression of ≥1% CPS is presented.

  6. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    PFS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants who had a PD-L1 strong positive expression of ≥10% CPS is presented.

  7. Overall Survival (OS) in All Participants [ Time Frame: Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants is presented.

  8. Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    OS was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants who had a PD-L1 positive expression of ≥1% CPS is presented.

  9. Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months) ]
    OS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants who had a PD-L1 strong positive expression of ≥10% CPS is presented.

  10. Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants [ Time Frame: Month 6 ]
    The PFS rate was determined in all participants at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.

  11. Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: Month 6 ]
    The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.

  12. Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: Month 6 ]
    The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.

  13. Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants [ Time Frame: Month 12 ]
    The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.

  14. Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: Month 12 ]
    The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.

  15. Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: Month 12 ]
    The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.

  16. Overall Survival Rate (OS Rate) at Month 6 in All Participants [ Time Frame: Month 6 ]
    The OS rate was determined for all participants at Month 6 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.

  17. Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: Month 6 ]
    The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.

  18. Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: Month 6 ]
    The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.

  19. Overall Survival Rate (OS Rate) at Month 12 in All Participants [ Time Frame: Month 12 ]
    The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.

  20. Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: Month 12 ]
    The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.

  21. Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: Month 12 ]
    The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.

  22. Programmed Cell Death Ligand 1 (PD-L1) Expression Status [ Time Frame: Day 1 ]
    PD-L1 expression status was determined as the percent of disease tumor cells, from newly obtained tumor biopsies, demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. The assay uses a Combined Positive Score (CPS) as a measure of PD-L1 positivity. The CPS is calculated as the number of PD-L1-positive cells divided by the number of viable tumor cells analyzed multiplied by 100. A CPS of <1% = negative; ≥1% = positive; and ≥10% = strongly positive. The number of participants categorized by PD-L1 CPS score is presented.

  23. Number of Participants Who Experienced At Least One Adverse Event (AE) [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months) ]
    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. These safety results are based on a 26-September-2018 data cutoff date.

  24. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months) ]
    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. These results are based on a 26-September-2018 data cutoff date.


Other Outcome Measures:
  1. Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in All Participants [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months) ]
    ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per modified RECIST is presented.

  2. Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months) ]
    ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥1% CPS and experienced a CR or PR per modified RECIST is presented.

  3. Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months) ]
    ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥10% CPS and experienced a CR or PR per modified RECIST is presented.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically- or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell and mixed transitional/non-transitional cell histologies)
  • Ineligible for cisplatin therapy
  • No prior systemic chemotherapy for metastatic disease (adjuvant or neoadjuvant platinum-based chemotherapy with recurrence >12 months since completion of therapy is allowed)
  • Available tissue from a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
  • Measureable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Adequate organ function
  • Female participants of childbearing potential have a negative urine or serum pregnancy test; surgically sterile, or willing to use 2 acceptable methods of birth control, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
  • Male participants must be willing to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study treatment

Exclusion Criteria:

  • Disease that is suitable for local therapy administered with curative intent
  • Currently participating or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study treatment
  • Prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to a previously administered agent
  • Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Evidence of interstitial lung disease or active non-infectious pneumonitis
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study treatment
  • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor
  • Known human immunodeficiency virus (HIV)
  • Known active Hepatitis B or C
  • Received a live virus vaccine within 30 days of planned start of study treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02335424


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:

Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02335424    
Other Study ID Numbers: 3475-052
2014-002206-20 ( EudraCT Number )
MK-3475-052 ( Other Identifier: Merck Protocol Number )
KEYNOTE-052 ( Other Identifier: Merck )
First Posted: January 9, 2015    Key Record Dates
Results First Posted: July 5, 2019
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
P-D1
PD-1
PD1
P-DL1
PD-L1
PDL-1
PDL1
Bladder cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents